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Biomedical subjects

M H Gault

Publications and source records attributed to M H Gault.

At least 19 recordsLinked to original sources
PubMed1992

Heparin, fatty acids and sodium, potassium-ATPase inhibition by plasma factors during hemodialysis.

To assess the relationship between heparin and the associated increase in nonesterified fatty acids (NEFA) and their possible influence on Na,K-ATPase during hemodialysis, we studied two groups of patients: (1) 12 patients on chronic hemodialysis dialysed with heparin and (2) 6 patients dialysed without heparin. All 12 patients who received heparin anticoagulation had a 7-fold rise in NEFA on average and also had an increase in circulating inhibitors of Na,K-ATPase assayed by 3H-ouabain displacement from Na,K-ATPase and/or by effect of plasma on the uptake of 86Rb by rat aortic rings. Serial assays in 3 of the patients receiving heparin showed NEFA and inhibitory changes to be at or near maximum within 30-60 min. Of the individual NEFA, the greatest relative increases were in oleic (18:1) and linoleic (18:2) acids, and the strongest correlations were between linoleic acid and both 3H-ouabain displacement (r = 0.94) and 86Rb uptake (r = 0.86). However, a small and slower increase in NEFA also occurred in 3 of the patients dialysed without heparin. We conclude that heparin anticoagulation during dialysis leads to a rapid and marked increase in circulating NEFA, particularly the unsaturated fatty acids, with a corresponding interference with Na,K-ATPase activity. The clinical significance of these findings is unknown. The rise in NEFA during dialysis without heparin in some patients suggests that factors other than heparin may also contribute to the rise in NEFA.

Adult↗
PubMed1992

Hemodialysis intravascular hemolysis and kinked blood lines.

Between May 29 and September 13, 1991, 4 patients developed acute intravascular hemolysis during hemodialysis with Monitral-S delivery systems and Hospal BSM A77 blood lines. All had malaise, nausea and headache; 3 had severe abdominal pain and 2 became very ill. Plasma hemoglobins were 3-21 g/l and LDH 542-3,300 IU in the 4 patients. Hepatoglobin became unmeasurable in 3 and was 0.09 g/l in the 4th patient. Soon afterwards, we found the arterial blood line tightly kinked at the dialyzer inlet port in the 4th patient and released it; he developed abdominal pain, hemolysis was present. We then found these lines had an extra long pump segment, and the rest was short and fitted poorly. When put in the first tubing organizer, severe kinking could occur just after the pump segment, causing back pressure but no alarm. We produced early visible hemolysis in a 1-liter circulating closed loop blood system with the blood line kinked either at the dialyzer inlet or just below the first arterial line tubing organizer with 40 g/l free plasma hemoglobin by 30 min. We excluded reported causes of intravascular hemolysis during hemodialysis. No hemolysis occurred before or during the 9 months after we discarded BSM A77 lines. The evidence indicates that kinked blood lines caused the hemolysis.

Hemolysis↗
PubMed1991

Comparison of patients with idiopathic calcium phosphate and calcium oxalate stones.

Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.

Acidosis, Renal Tubular↗
PubMed1990

The diagnosis and prognosis of autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. METHODS: We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. RESULTS: In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. CONCLUSIONS: At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life.

Adult↗
PubMed1990

Charcot-Marie-Tooth disease and nephropathy in a mother and daughter with a review of the literature.

We report a mother-and-child combination of Charcot-Marie-Tooth disease and nephropathy. The mother received a cadaveric renal transplant, and the daughter has heavy proteinuria with normal glomerular filtration rate. There have been 7 single case reports of both disease entities and 1 report of 3 patients which includes the only sib pair. The related literature is reviewed.

Adolescent↗
PubMed1990

Comparison of urinary tract infection in calcium oxalate and calcium phosphate stone formers.

To compare the frequency of urine infection in calcium oxalate and calcium phosphate stone formers, we reviewed charts from patients whose last renal stone submitted for analysis was predominantly composed of calcium phosphate in 118 and of calcium oxalate in 223. Positive cultures were commoner, but not significantly, in the phosphate than the oxalate stone formers, both in men (17 vs. 7.6%) and women (22 vs. 15%). Bacteria frequently producing urease were found in only 4% of the phosphate group. Urine leucocytes were slightly more frequent in the oxalate group for men and significantly so for women. The results do not support the concept that calcium phosphate stones are mainly due to infection with urease-producing or other bacteria.

Calcium Oxalate↗
PubMed1990

Plasma conjugated androgens in a dialysis-dependent male as immunoreactive digitalis-like factors.

Endogenous digitalis-like factors (DLF) including those which were immunoreactive with digoxin antibody and those which displaced ouabain from Na,K-ATPase, were isolated from the plasma of a dialysis-dependent male patient not taking digoxin. Plasma was passed through a C18 disposable column, the DLF eluted with methanol and separated by HPLC on a C8 column. Immunoreactive DLF were measured in each 1 ml HPLC fraction using radioimmunoassay (RIA) for digoxin. The immunoreactive peaks were determined and aliquots from each peak analyzed by fast atom bombardment mass spectroscopy (FAB-ms). The compounds in the five major HPLC immunoreactive peaks were identified as: 1) dehydroepiandrosterone glucuronide and tetrahydrocortisone glucuronide; 2) epiandrosterone glucuronide; 3) dehydroepiandrosterone sulfate and androsterone glucuronide; 4) epiandrosterone sulfate and 5) androsterone sulfate and androstanediol glucuronide. These immunoreactive DLF represent 70% of the total plasma immunoreactive DLF of 0.124 micrograms digoxin equivalents/l. Aliquots of the HPLC fractions were also assayed for ability to displace ouabain from Na,K-ATPase. The ouabain displacing DLF gave a very different elution pattern from that obtained by RIA with the major Na,K-ATPase ouabain displacing DLF eluting in the more polar fractions. They remain unidentified.

Adult↗
PubMed1989

Lipids as endogenous Na,K-ATPase inhibitors in plasma of healthy individuals and in dialysis dependent patients.

We assayed plasma Na,K-ATPase inhibitory activity due to total lipids and lipid fractions. The effect of dialysis on the Na,K-ATPase inhibitory activity was also studied. Plasma lipid extracts from 11 healthy volunteers and 9 dialysis-dependent patients (pre and post dialysis) were separated into neutral lipids and phospholipids. Further fractionation was by thin layer chromatography. These lipid fractions were analyzed for Na,K-ATPase inhibitory activity by displacement of [3H]-ouabain from hog brain Na,K-ATPase. Total inhibitory activity was significantly increased (p less than 0.001) in the post-dialysis plasma compared to pre-dialysis plasma of the same patient group and to controls (482, 85 and 78 nmol/L respectively; means of the groups in digoxin equivalents). The major inhibitory activity was associated with non-esterified fatty acids with modest contributions from four other lipid fractions. Our results show that endogenous lipids are major plasma Na,K-ATPase inhibitors in vitro under these assay conditions.

Adult↗
PubMed1989

The kidney-ureter stone sexual paradox: a possible explanation.

The greater frequency of renal stones seen on excretory urograms in women, compared with the greater frequency of ureteral stones in men has been termed a sexual paradox. We assessed stone composition and weight, and sex as possible explanatory factors. A total of 4,014 renal and ureteral calculi was analyzed. For the 3,119 calculi in which only calcium oxalate and/or phosphate was detected by infrared and wet chemical analysis, there was a strong relationship between the oxalate-to-phosphate weight ratio and sex (p less than 0.0001). The mean weight for phosphate stones was 330 mg. but for oxalate stones it was 107 mg. Male-to-female ratios were 2.7, 2.2 and 1.8 for stone weight groups of 20 or less, 21 to 100 and more than 100 mg. The male-to-female ratio was 0.87 for the 171 stones containing magnesium ammonium phosphate; the average weight was 508 mg. for men and 1,560 mg. for women. The tendency for phosphate stones to be heavier and relatively more common in women compared to predominantly oxalate stones may partly account for the sexual paradox.

Calcium Oxalate↗
PubMed1989

Development of a health questionnaire specific for end-stage renal disease.

To compare the efficacy of various end-stage renal disease (ESRD) therapies valid and reproducible probes which measure well-being and are specific for ESRD are necessary. Four studies were undertaken to provide and test these probes. (1) 107 dialysis and 119 transplant recipients were interviewed to determine the prevalence of 24 physical symptoms. (2) A questionnaire was devised using 2 new indexes (a symptom scale derived from the first study using 12 symptoms and an affect scale comprising 12 emotions) and 6 indexes previously used in other chronic illnesses. Interobserver and intraobserver reproducibility was satisfactory. (3) Construct validity for the questionnaire was shown by interviewing 97 dialysis and 82 transplant patients in whom we hypothesized that physical well-being would be better in transplant patients. After age matching the transplant group was more active, with a higher objective quality of life and fewer physical symptoms than the dialysis group. (4) 63 stable dialysis, 67 stable transplant, 15 dialysis patients successfully transplanted in the intervening year and 5 failed transplanted patients were reinterviewed 1 year later to assess the responsiveness of the questionnaire. In the group who had recently been successfully transplanted both physical, affect and quality of life scores showed a major improvement following transplant. We conclude that this questionnaire is specific for ESRD, examines physical, psychological, and social well-being, is brief, easily administered, reproducible, has construct validity and is responsive to changes in therapy.

Adult↗
PubMed1988

Left ventricular hypertrophy in end-stage renal disease.

To determine the prevalence of left ventricular hypertrophy (LVH; left ventricular wall thickness greater than or equal to 1-2 cm in diastole) among end-stage renal disease (ESRD) patients and the most important risk factors that independently relate to LVH, 189 non-diabetic ESRD patients without dilated cardiomyopathy in two centres had echocardiography and full clinical review. 104 of 189 (55%) patients had LVH consisting of 52 of 83 (65%) patients on haemodialysis, 18 of 20 (90%) peritoneal dialysis patients and 34 of 86 (40%) transplanted patients. Using multiple logistic regression, the most important factors which independently related to LVH, in all patients studied, were dialysis as current ESRD treatment (p less than 0.001), followed by age (p = 0.008), hypertension as defined by number of blood pressure medications (p = 0.007), followed by high serum alkaline phosphatase which probably reflects hyperparathyroidism (p = 0.03). In a subset of patients with severe LVH (left ventricular wall thickness greater than or equal to 1.4 cm), a high serum alkaline phosphatase level was the best predictor of LVH (p less than 0.001), followed by high diastolic blood pressure (p = 0.004) and age (p = 0.02). In dialysis patients, the most important variable were age (p = 0.009) and high serum alkaline phosphatase (p = 0.03). In the transplant group, patients with LVH were taking significantly more antihypertensive medications than those without LVH (p = 0.002). This variable was the only predictor of LVH in the transplant group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Spurious stones.

One hundred and sixteen (3.5%) of 3,300 specimens submitted by 72 patients as urinary stones were artifacts, i.e. not formed of accepted constituents of urinary calculi. The laboratory diagnostic methods included infrared and wet chemical analysis, and X-ray diffraction. Twenty-eight were of organic origin and some of these were undoubtedly submitted by accident as calculi. Eighty-eight were of mineral origin, mainly quartz and feldspar, and it is believed that the great majority were submitted for secondary gain or for psychiatric reasons. Ten patients each submitted from 2 to 10 artifacts. Five cases studies are presented which illustrate some confounding clinical and laboratory findings. Spurious stones can lead to difficult clinical and laboratory problems.

Adult↗
PubMed1988

Clinical features and severity of nonspecific symptoms in dialysis patients.

Nonspecific symptoms are common in dialysis patients but few methods are available to measure their severity and their response to alteration in dialysis therapy. To determine the clinical features and measure the severity of the most important symptoms in end-stage renal disease (ESRD) patients, 97 dialysis patients were interviewed, 63 of whom were reinterviewed 1 year later. For comparison 82 transplant recipients were also interviewed. The six most important symptoms in dialysis patients (using the product of the patient's perception of severity and prevalence) were tiredness, cramps, pruritus, dyspnea, headaches and joint pain. The symptoms were long-standing, occurred frequently, with little difference in prevalence between hemo- and peritoneal dialysis patients, and were often unrelated to a hemodialysis session. For each symptom, several dimensions of severity were assessed including frequency, duration, effect on sleep, daily living, activity, subjective quality of life and necessity for drug therapy. Often these dimensions did not correlate with patient's perception of severity. For each symptom these items were combined to give an aggregate score with a range 0-10. Interobserver reproducibility for each symptom score was greater than or equal to 0.7 but intraobserver reproducibility was poor for 3 symptoms, because of the fluctuating nature of the symptoms. Construct validity was demonstrated by finding a significantly worse distribution of aggregate scores for tiredness, cramps, pruritus, dyspnea and nausea/vomiting in dialysis compared to transplant patients. Aggregate scores changed little after 1 year's follow-up in stable dialysis patients but significant improvement in the aggregate scores for tiredness, dyspnea and nausea/vomiting were observed in 14 patients after successful transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude to Health↗